CORTRD1
MCID: CRT065
MIFTS: 25

Cortisone Reductase Deficiency 1 (CORTRD1)

Categories: Endocrine diseases, Genetic diseases, Metabolic diseases

Aliases & Classifications for Cortisone Reductase Deficiency 1

MalaCards integrated aliases for Cortisone Reductase Deficiency 1:

Name: Cortisone Reductase Deficiency 1 56 12 73 29 13 6 71
Cortrd1 56 12 73
Cortisone Reductase Deficiency, Type 1 39

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive


HPO:

31
cortisone reductase deficiency 1:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0090141
OMIM 56 604931
OMIM Phenotypic Series 56 PS604931
MeSH 43 D008661
NCIt 49 C131849
MedGen 41 C3551716
UMLS 71 C3551716

Summaries for Cortisone Reductase Deficiency 1

OMIM : 56 Cortisone reductase deficiency (CRD) results from a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11-beta-hydroxysteroid dehydrogenase (HSD11B1; 600713). The oxoreductase activity of 11-beta-HSD requires the NADPH-regenerating enzyme hexose-6-phosphate dehydrogenase (H6PD; 138090) within the endoplasmic reticulum. Lack of cortisol regeneration stimulates ACTH-mediated adrenal hyperandrogenism, with males manifesting in early life with precocious pseudopuberty and females presenting in midlife with hirsutism, oligomenorrhea, and infertility. Biochemically, CRD is diagnosed through the assessment of urinary cortisol and cortisone metabolites and consists of measuring the tetrahydrocortisol (THF) plus 5-alpha-THF/tetrahydrocortisone (THE) ratio, which in CRD patients is typically less than 0.1 (reference range, 0.7 to 1.2) (summary by Lavery et al., 2008). (604931)

MalaCards based summary : Cortisone Reductase Deficiency 1, also known as cortrd1, is related to cortisone reductase deficiency 2. An important gene associated with Cortisone Reductase Deficiency 1 is H6PD (Hexose-6-Phosphate Dehydrogenase/Glucose 1-Dehydrogenase). Affiliated tissues include pituitary and ovary, and related phenotypes are obesity and precocious puberty

Disease Ontology : 12 A cortisone reductase deficiency that is characterized by failure to regenerate cortisol via the enzyme 11-beta-hydroxysteroid dehydrogenase which requires NADPH regeneration by hexose-6-phosphate dehydrogenase, resulting in ACTH-mediated adrenal hyperandrogenism. It has material basis in autosomal recessive inheritance of homozygous or compound heterozygous mutation in the hexose-6-phosphate dehydrogenase gene (H6PD) on chromosome 1p36.

UniProtKB/Swiss-Prot : 73 Cortisone reductase deficiency 1: An autosomal recessive error of cortisone metabolism characterized by a failure to regenerate cortisol from cortisone, resulting in increased cortisol clearance, activation of the hypothalamic- pituitary axis and ACTH-mediated adrenal androgen excess. Clinical features include hyperandrogenism resulting in hirsutism, oligo- amenorrhea, and infertility in females and premature pseudopuberty in males.

Related Diseases for Cortisone Reductase Deficiency 1

Diseases related to Cortisone Reductase Deficiency 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 cortisone reductase deficiency 2 11.3

Symptoms & Phenotypes for Cortisone Reductase Deficiency 1

Human phenotypes related to Cortisone Reductase Deficiency 1:

31 (show all 6)
# Description HPO Frequency HPO Source Accession
1 obesity 31 HP:0001513
2 precocious puberty 31 HP:0000826
3 acne 31 HP:0001061
4 infertility 31 HP:0000789
5 oligomenorrhea 31 HP:0000876
6 hirsutism 31 HP:0001007

Symptoms via clinical synopsis from OMIM:

56
Growth Weight:
obesity
central fat distribution

Genitourinary Internal Genitalia Female:
infertility
oligomenorrhea

Endocrine Features:
hyperandrogenism
delayed conversion of oral cortisone acetate to plasma cortisol
low tetrahydrocortisol (thf) plus 5-alpha-thf/tetrahydrocortisone (the) ratio
low urinary cortols-to-cortolone ratio
low to normal level of cortisol metabolites
more
Skin Nails Hair Skin:
acne

Skin Nails Hair Hair:
hirsutism
androgenic alopecia (in some patients)

Genitourinary External Genitalia Male:
precocious puberty, gonadotropin-independent

Clinical features from OMIM:

604931

Drugs & Therapeutics for Cortisone Reductase Deficiency 1

Search Clinical Trials , NIH Clinical Center for Cortisone Reductase Deficiency 1

Genetic Tests for Cortisone Reductase Deficiency 1

Genetic tests related to Cortisone Reductase Deficiency 1:

# Genetic test Affiliating Genes
1 Cortisone Reductase Deficiency 1 29 H6PD

Anatomical Context for Cortisone Reductase Deficiency 1

MalaCards organs/tissues related to Cortisone Reductase Deficiency 1:

40
Pituitary, Ovary

Publications for Cortisone Reductase Deficiency 1

Articles related to Cortisone Reductase Deficiency 1:

(show all 11)
# Title Authors PMID Year
1
Steroid biomarkers and genetic studies reveal inactivating mutations in hexose-6-phosphate dehydrogenase in patients with cortisone reductase deficiency. 56 6
18628520 2008
2
Lack of Association of the 11beta-hydroxysteroid dehydrogenase type 1 gene 83,557insA and hexose-6-phosphate dehydrogenase gene R453Q polymorphisms with body composition, adrenal androgen production, blood pressure, glucose metabolism, and dementia. 56 6
17062770 2007
3
Variants implicated in cortisone reductase deficiency do not contribute to susceptibility to common forms of polycystic ovary syndrome. 56 6
16817821 2006
4
Genotypes at 11beta-hydroxysteroid dehydrogenase type 11B1 and hexose-6-phosphate dehydrogenase loci are not risk factors for apparent cortisone reductase deficiency in a large population-based sample. 56 6
16091483 2005
5
Mutations in the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase interact to cause cortisone reductase deficiency. 56 6
12858176 2003
6
Apparent cortisone reductase deficiency: a rare cause of hyperandrogenemia and hypercortisolism. 56 6
11150889 2000
7
Apparent cortisone reductase deficiency: a functional defect in 11beta-hydroxysteroid dehydrogenase type 1. 56 6
10522997 1999
8
A study of the hexose-6-phosphate dehydrogenase gene R453Q and 11beta-hydroxysteroid dehydrogenase type 1 gene 83557insA polymorphisms in the polycystic ovary syndrome. 6
15827106 2005
9
Apparent cortisone reductase deficiency: a unique form of hypercortisolism. 56
8923828 1996
10
Defects in the HSD11 gene encoding 11 beta-hydroxysteroid dehydrogenase are not found in patients with apparent mineralocorticoid excess or 11-oxoreductase deficiency. 56
8370690 1993
11
A new defect in the peripheral conversion of cortisone to cortisol. 56
3990293 1985

Variations for Cortisone Reductase Deficiency 1

ClinVar genetic disease variations for Cortisone Reductase Deficiency 1:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 H6PD NM_004285.4(H6PD):c.960G>A (p.Val320=)SNV Pathogenic 31584 rs398122816 1:9322332-9322332 1:9262273-9262273
2 H6PD NM_004285.4(H6PD):c.1076G>A (p.Gly359Asp)SNV Pathogenic 31585 rs387907167 1:9323628-9323628 1:9263569-9263569
3 H6PD NM_004285.4(H6PD):c.948C>G (p.Tyr316Ter)SNV Pathogenic 31586 rs398122817 1:9322320-9322320 1:9262261-9262261
4 H6PD NM_004285.4(H6PD):c.325del (p.Arg109fs)deletion Pathogenic 31587 rs398122818 1:9305317-9305317 1:9245258-9245258
5 H6PD NM_004285.4(H6PD):c.1860_1861insACAGGTGGTTGACCTGTGGCCGGGTCTGA (p.Glu621delinsThrGlyGlyTer)insertion Pathogenic 16130 rs606231222 1:9324412-9324413 1:9264353-9264354
6 H6PD NM_004285.4(H6PD):c.1358G>A (p.Arg453Gln)SNV Uncertain significance 16131 rs6688832 1:9323910-9323910 1:9263851-9263851
7 H6PD NM_004285.4(H6PD):c.745+88T>ASNV Benign 191261 rs12032814 1:9307230-9307230 1:9247171-9247171

UniProtKB/Swiss-Prot genetic disease variations for Cortisone Reductase Deficiency 1:

73
# Symbol AA change Variation ID SNP ID
1 H6PD p.Arg453Gln VAR_026487 rs6688832
2 H6PD p.Pro146Leu VAR_069193

Expression for Cortisone Reductase Deficiency 1

Search GEO for disease gene expression data for Cortisone Reductase Deficiency 1.

Pathways for Cortisone Reductase Deficiency 1

GO Terms for Cortisone Reductase Deficiency 1

Sources for Cortisone Reductase Deficiency 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
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30 HMDB
31 HPO
32 ICD10
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43 MeSH
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53 NINDS
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56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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